CN103865795A - Microfluidic chip for controlling cell sorting via voltage - Google Patents
Microfluidic chip for controlling cell sorting via voltage Download PDFInfo
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- CN103865795A CN103865795A CN201410113120.2A CN201410113120A CN103865795A CN 103865795 A CN103865795 A CN 103865795A CN 201410113120 A CN201410113120 A CN 201410113120A CN 103865795 A CN103865795 A CN 103865795A
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- sodium alginate
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/16—Microfluidic devices; Capillary tubes
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/02—Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/40—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure
Abstract
The invention relates to a microfluidic chip for controlling cell sorting via a voltage, and belongs to the field of the microfluidic chips. The microfluidic chip comprises a fluidic drop generating part, a charging part, a voltage controlling part and a fluidic drop collecting part, wherein the fluidic drop generating part comprises a sodium alginate channel and an oil channel which are perpendicular; the charging part comprises the sodium alginate channel and charging electrodes distributed at two sides of the sodium alginate channel; the voltage controlling part comprises two sodium alginate subchannels which are connected with the sodium alginate channels, wherein a triangular wedge is arranged at the connecting point of the sodium alginate subchannels and the sodium alginate subchannels; the charging electrodes are distributed at two sides of the sodium alginate subchannels; the sodium alginate subchannels are connected with an oil injecting pipeline before entering the charging electrodes. According to the microfluidic chip, fluidic drops are charged, so that the voltage required by the cell sorting is greatly reduced, and thus the reaction time required by the voltage from zero to a peak value is shortened, and the sorting controllability is greatly improved.
Description
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Technical field
The present invention relates to a kind of micro-fluidic chip of voltage control sorting cells, belong to micro-fluidic chip field.
Background technology
Based on the micro-fluidic chip of drop, have lot of advantages, for example: high-level efficiency, consume reagent few, pollution-free, fast, volume is little etc. in response.Drop micro-fluidic chip became the most promising experiment porch in chemistry and biological study in the last few years, and it is operation and the analysis one row of individual cells and effective ways.The drop injecting can be cut apart separately, mixes, and transport, catches and sorting.There is at present the method for much drop being processed, for example: based on the method for Principles of Acoustics, utilize the method for electromagnetism, the method based on electricity etc.Wherein electrical method is because its reaction times is short, thereby easily carries out and well compatible this series of advantages becomes a kind of the most promising method that drop is operated.
Method based on electricity so far, researchist used: dielectrophoresis method (DEP), Electrowetting, electrostatic operation method etc. separates, merges drop, efficient separation or obtain a drop service platform.It is succinct, efficient, easy to operate, pollution-free that above-mentioned whatsoever method does not all reach simultaneously.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of micro-fluidic chip that can succinctly efficiently carry out sorting to cell.
The micro-fluidic chip providing of the present invention, comprises drop generating unit, charging part, voltage control division and drop collection unit;
Described drop generating unit comprises sodium alginate passage and the oily passage with sodium alginate channel vertical;
Described charging part comprises sodium alginate passage and is distributed in the charging electrode of sodium alginate passage both sides;
Described voltage control division comprises two sodium alginate subchannels, be all connected with sodium alginate passage, and tie point has a trilateral wedge; Article two, the both sides of the sodium alginate subchannel charging electrode that all distributes, and sodium alginate subchannel connected an oiling pipeline before entering charging electrode;
Described drop collection unit comprises conduit and collection container, and described conduit is connected with sodium alginate subchannel.
What in sodium alginate passage and sodium alginate subchannel, flow is the sodium alginate suspension that is mixed with cell, and what in oily passage, flow is silicone oil.
In drop generating unit, inject silicone oil from oily passage, as external phase, inject the sodium alginate suspension (hereinafter to be referred as SA) of cell mixing from sodium alginate passage, as disperse phase, wanting of the velocity ratio SA of oil is fast, thereby can obtain SA drop by pinch off SA, by controlling the flow velocity of oil and SA, can the accurate size of controlling drop.
Charging part can make the sodium alginate drop that contains cell produce induced charge.
Charging part utilization adds electric field, in non-contacting mode, SA drop is carried out to precharge.In the time that a neutral solution drip is crossed the charging electric field in micro-raceway groove, can induction produce positive and negative charge on drop surface.Sodium alginate channel end (place crossing with sodium alginate subchannel) has a wedge, in order to the SA drop separation after charging is become to the sub-drop with positive and negative different electric charges respectively.By precharge operation, separation voltage and switching time are significantly reduced.
Voltage control division can be controlled charged drop direction of motion and then can enter predefined passage.
In voltage control division, sodium alginate subchannel upstream portion (before connecting oiling pipeline) is narrow, downstream part (after connecting oiling pipeline) is wider, drop can change to wide pipeline speed from narrow pipeline, may make drop below knock above, so need to avoid the device of collision, wherein oiling pipeline can be used for changing SA liquid drop movement speed and solve above-mentioned collision problem.
Charging electrode in charging part and voltage control division is symmetrically, can produce uniform electric field in channel part.Electrode forms by inject temperature silver slurry in electrode raceway groove, and electrode height is the same with channel height.Do like this and electrode and microfluidic channel can be accomplished in one deck, thereby simplified the making processes of chip.
Drop collection unit is collected the drop obtaining after sorting.
Specific to one embodiment of the present of invention, what in sodium alginate passage and sodium alginate subchannel, flow is the sodium alginate suspension that is mixed with human breast cancer cell (MCF-7).
Preferred as one, sodium alginate channel width 50 μ m in micro-fluidic chip of the present invention, the upstream width of sodium alginate subchannel is 100 μ m, downstream width is 200 μ m.
The sodium alginate passage of the charging part of flowing through requires narrow, is because wish that drop width is consistent with passage width, is full of passage, thus not deflection of drop when making charging.Sodium alginate subchannel downstream is wide is because control part requirement passage is suitably wider, provides a horizontal space to carry out deflection to drop.
When micro-fluidic chip work of the present invention, pass through microscope, can observe a series of stream of liquid droplets superpotential control part, in the time that the SA stream of liquid droplets with MCF-7 is come, on charging electrode in voltage control division, add an instantaneous high pressure pulse, thereby drop meeting deflection under the effect of pulse enters the target cell collection unit of setting, reaches the object of specific cell being carried out to sorting.
Compare the technology of existing sorting cells, the present invention is by being integrated together electrode raceway groove and micro-fluidic chip liquid-flow raceway groove, make the micro-fluidic sorting chip of simple individual layer, and the electrode that traditional electric sorting micro-fluidic chip uses normally plates the corresponding precious metal of one deck by the method for magnetron sputtering or evaporation on slide glass, for traditional sorting chip, this kind of chip manufacturing process is simple and easy, and equipment is simple, material cheapness, pollution-free.
Meanwhile, the raceway groove that the electrode of this fabrication techniques passes through with fluid has identical height, is 3 D stereo, thereby the electric field being formed in the middle of electrode is uniformly, compares traditional die, is easier to drop charge and control.
Apparatus of the present invention are by charging to drop, needed voltage (being reduced to 30V from 300V) while greatly having reduced sorting, thereby reduce voltage from zero to the needed reaction times of peak value, greatly improve the controllability of sorting, reduced the voltage peak of pulse also for certain basis has been established in following miniaturization development.
Brief description of the drawings
The structure composition of the micro-fluidic chip of Fig. 1 sorting cells, wherein:
1-drop generating unit, 2-charging part, 3-voltage control division, 4-drop collection unit, 5-sodium alginate passage, 6-oil passage, 7-charging electrode, 8-sodium alginate subchannel, 9-wedge, 10-oiling pipeline, 11-conduit, 12-collection container.
Fig. 2 micro-fluidic chip working state figure.
Embodiment
The micro-fluidic chip of realizing sorting cells by controlling voltage of the present invention, comprises drop generating unit 1, charging part 2, voltage control division 3 and drop collection unit 4;
Described drop generating unit 1 comprises sodium alginate passage 5 and the oily passage 6 with sodium alginate channel vertical;
Described charging part 2 comprises sodium alginate passage 5 and is distributed in the charging electrode 7 of sodium alginate passage 5 both sides;
Described voltage control division 3 comprises two sodium alginate subchannels 8, be all connected with sodium alginate passage 5, and tie point has a trilateral wedge 9; Article two, the both sides of sodium alginate subchannel 8 charging electrode 7 that all distributes, and sodium alginate subchannel 8 connected an oiling pipeline 10 before entering charging electrode 7;
Described drop collection unit 4 comprises conduit 11 and collection container 12, and described conduit 11 is connected with sodium alginate subchannel 8.
What 8 li of sodium alginate passage 5 and sodium alginate subchannels were mobile is the sodium alginate suspension that is mixed with cell, and what 6 li, oily passage was mobile is silicone oil.
In micro-fluidic chip of the present invention, sodium alginate passage 5 and sodium alginate subchannel 8 are highly 60 μ m.The wide 50 μ m of sodium alginate passage 5, wedge 9 height and width are respectively 70 μ m and 55 μ m.The long 400 μ m of charging electrode 7 in voltage control division, aspect ratio sodium alginate subchannel height is slightly high to ensure that the electric field in sodium alginate subchannel is uniform.Charging electrode 7 and sodium alginate subchannel spacing are 100 μ m.
The wide 200 μ m of conduit 11.
Micro-fluidic chip of the present invention is to make by the soft lithographic method of standard.First, template figure is drawn with Coreldraw according to the chip structure of describing before.Then on silicon chip, plate one deck SU-8 2050 photoresist material moulds.Obtaining PDMS layer and irreversible it be tied to glass two rear flank with oxygen plasma, micro-fluidic chip is placed on and roastingly at 120 DEG C within 2 hours, strengthens hydrophobicity and eliminate residual water.
Micro-fluidic chip of the present invention, wherein charging electrode is that silver by inject moderate temperature in electrode raceway groove slurry forms, electrode height is the same with channel height.
When micro-fluidic chip of the present invention uses, connect a voltage control system.Voltage control system comprises that high-voltage pulse produces the Android mobile applications of circuit and this pulse of control.The amplitude of its pulse, width, time length can accurately be controlled by smart mobile phone.
An application example of micro-fluidic chip of the present invention, wherein the flow velocity of oil droplet is 140 μ L/h, being mixed with human breast cancer cell and erythrocytic sodium alginate flow rate of liquid is 20 μ L/h.At this time droplet dia is 50 μ m.
In charging part, charging voltage is 1500V, and in voltage control division, sorting peak value of pulse is 30V, and pulse operating time is 100ms.When examining under a microscope, to be enclosed with human breast cancer cell's's (human breast cancer cell's size more doubly than the large 5-10 of red corpuscle) stream of liquid droplets out-of-date, on the charging electrode of voltage control division, add a momentary impulse, at this time this specific charged drop is subject to electrical forces effect under electric field, will turn to a lateral deviation, flow to specific collection unit, arrive sorting sorting human breast cancer cell's object.As shown in Figure 2.
Claims (5)
1. a micro-fluidic chip for voltage control sorting cells, is characterized in that, comprises drop generating unit (1), charging part (2), voltage control division (3) and drop collection unit (4);
Described drop generating unit (1) comprises sodium alginate passage (5) and the oily passage (6) vertical with sodium alginate passage (5);
Described charging part (2) comprises sodium alginate passage (5) and is distributed in the charging electrode (7) of sodium alginate passage (5) both sides;
Described voltage control division (3) comprises two sodium alginate subchannels (8), be all connected with sodium alginate passage (5), and tie point has a trilateral wedge (9); Article two, the both sides of sodium alginate subchannel (8) charging electrode (7) that all distributes, and sodium alginate subchannel (8) connects an oiling pipeline (10) before entering charging electrode (7);
Described drop collection unit (4) comprises conduit (11) and collection container (12), and described conduit (11) is connected with sodium alginate subchannel (8).
2. micro-fluidic chip according to claim 1, is characterized in that, sodium alginate passage (5) and sodium alginate subchannel (8) inner flow be the sodium alginate suspension that is mixed with human breast cancer cell.
3. micro-fluidic chip according to claim 1 and 2, is characterized in that, the wide 50 μ m of sodium alginate passage (5), and the upstream width of sodium alginate subchannel (8) is 100 μ m, downstream width is 200 μ m.
4. micro-fluidic chip according to claim 1 and 2, is characterized in that, sodium alginate passage (5) and sodium alginate subchannel (8) are highly 60 μ m.
5. micro-fluidic chip according to claim 1 and 2, is characterized in that, wedge (9) height and width are respectively 70 μ m and 55 μ m.
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| CN201410113120.2A CN103865795B (en) | 2014-03-25 | 2014-03-25 | Microfluidic chip for controlling cell sorting via voltage |
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| CN103865795B CN103865795B (en) | 2015-06-03 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105486865A (en) * | 2014-09-15 | 2016-04-13 | 浙江大学 | Micro-fluidic chip used for cell sorting and gathering and application of micro-fluidic chip |
| CN108020490A (en) * | 2017-06-23 | 2018-05-11 | 中国科学院天津工业生物技术研究所 | A kind of high flux screening equipment using drop micro-fluidic chip |
| CN109735429A (en) * | 2019-01-28 | 2019-05-10 | 佛山市铬维科技有限公司 | Micro-fluidic chip and the system and its separation method for separating various kinds of cell |
| CN111760600A (en) * | 2020-06-23 | 2020-10-13 | 深圳技术大学 | Microfluidic chip, preparation method thereof and cell sorting method |
| WO2022227853A1 (en) * | 2021-04-27 | 2022-11-03 | 京东方科技集团股份有限公司 | Microfluidic chip, box body device, and microfluidic device |
| WO2024036549A1 (en) * | 2022-08-18 | 2024-02-22 | 京东方科技集团股份有限公司 | Microfluidic chip and microfluidic device |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101250483B (en) * | 2008-04-11 | 2011-04-13 | 重庆大学 | Combined splint microelectrode type micro-fluidic dielectrophoresis cell separation and enrichment chip |
| CN102008983B (en) * | 2010-11-01 | 2012-08-08 | 武汉大学 | Microfluidic chip suitable for producing microcapsules |
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2014
- 2014-03-25 CN CN201410113120.2A patent/CN103865795B/en active Active
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105486865A (en) * | 2014-09-15 | 2016-04-13 | 浙江大学 | Micro-fluidic chip used for cell sorting and gathering and application of micro-fluidic chip |
| CN105486865B (en) * | 2014-09-15 | 2017-04-19 | 浙江大学 | Micro-fluidic chip used for cell sorting and gathering and application of micro-fluidic chip |
| CN108020490A (en) * | 2017-06-23 | 2018-05-11 | 中国科学院天津工业生物技术研究所 | A kind of high flux screening equipment using drop micro-fluidic chip |
| CN109735429A (en) * | 2019-01-28 | 2019-05-10 | 佛山市铬维科技有限公司 | Micro-fluidic chip and the system and its separation method for separating various kinds of cell |
| CN111760600A (en) * | 2020-06-23 | 2020-10-13 | 深圳技术大学 | Microfluidic chip, preparation method thereof and cell sorting method |
| CN111760600B (en) * | 2020-06-23 | 2021-05-25 | 深圳技术大学 | Microfluidic chip, preparation method thereof and cell sorting method |
| WO2022227853A1 (en) * | 2021-04-27 | 2022-11-03 | 京东方科技集团股份有限公司 | Microfluidic chip, box body device, and microfluidic device |
| WO2024036549A1 (en) * | 2022-08-18 | 2024-02-22 | 京东方科技集团股份有限公司 | Microfluidic chip and microfluidic device |
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| CN103865795B (en) | 2015-06-03 |
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